Derivation of Human Embryonic Stem Cells (hESC)

The Ethics Advisory Board of the ISSCR has been asked to reflect on the ethics of several new kinds of research to produce hESC. This research uses methods other than the now-established standard of practice, developed in 1998 by Dr. James Thompson (University of Wisconsin), of generating hESC by culturing the inner cell mass of blastocysts at the 4- to 5-day stage of development. In particular we have been asked about the new reports of hESC derivation using blastomeres from an 8-cell embryo in a process normally used for pre-implantation genetic diagnosis (PGD). With this approach, one cell is removed from the developing embryo and the remaining 7 cells are allowed to develop into a blastocyst. This is reported to have been done in mouse embryos.

1) In this, as in any scientific area, first reports are only first reports. They must be replicated in other labs initially with mouse embryos and then with human cells. There have been many press accounts of exciting new research with far fewer peer reviewed claims and even fewer verifiable and replicable breakthroughs.

2) The President’s Bioethics Council, in its consideration of this possibility, has noted that the primary embryo, which presumably is destined for development to term, would be subjected to a non-therapeutic procedure that entails an unknown level of risk. In PGD the risk is taken for the "benefit" of the embryo as the goal is to select an embryo that is free of grave, inherited genetic disease. However, if the blastomere is only being removed for the creation of a new stem cell line, the risk is entirely for the world of science. Although the risks associated with PGD are considered to be very low, using this technology for the generation of new hESC lines would raise a new set of issues for parents that would have to be carefully considered.

3) While some may be comforted by the fact that the primary embryo can continue on in its development, some opponents of hES cell research will see the blastomere as just another totipotent cell, and as such, the moral equivalent of a baby, regardless of whether it is cultured in a fashion that forces its development directly toward a hESC. It remains to be determined if the blastomere is totipotent, able to generate an entire blastocyst or pluripotent, only able to give rise to ES cells. To explore such an issue raises yet another set of troubling ethical issues. It has long been considered impermissible to artificially create identical twins by embryo splitting in the IVF process and this could be seen as a variant of that problem.

4) The proposal that embryo biopsy be used to derive pluripotent embryonic stem cells would present a complex and novel scenario for the couple undergoing assisted reproductive therapies, who would simultaneously have to give consent to embryo creation for both reproductive purposes and research. This is not contemplated in the NRC/IOM guidelines, which envision a separation between the two decisions. Clearly, the couple would have to be assured that any decision concerning donation of a blastomere for research would not affect their IVF treatment. Other implications for the consent process require further thought.

5) We encourage all aspects of scientific advancement if it helps to foster support for this important realm of science, but also appreciate that breakthroughs must be scientifically sound and able to be replicated. We must clearly emphasize that the technique for stem cell derivation from biopsied blastomeres represents a speculative supplemental but not substitute path for proceeding internationally with the use of embryonic cells. We are concerned that substantive research not be halted or impeded as this or other pursuits are tried.

6) The objective of all of this research must be to achieve the best scientific and therapeutic results. While social consensus is desirable, scientific advances are guided by the important questions of science and not by ideological or political considerations. That being noted, we are supportive of all genuine efforts to move the science forward. We are all encouraged by any findings that show a promise of effectiveness for scientific and medical purposes. Those of us who find hESC technologies acceptable see no obvious ethical problems with the use of embryo biopsy, if it is safe and effective. We wish to reiterate that this may be an exciting research result, but it needs to be replicated in mice and attempted in humans. It is just one of many promising strategies to be pursued simultaneously.

Laurie S. Zoloth, Ph.D., R. Alta Charo, J.D., Henry T. Greely, J.D., Suzanne Holland, Ph.D., Cynthia B. Cohen, J.D., Ph.D., LeRoy B. Walters, Ph.D., Jonathan D. Moreno, Ph.D.

Posted: July 12, 2005